COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Intermittent PI3Ko inhibition sustains anti-tumor immunity and curbs irAEs

YesPhosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

Effect of the aqueous extract of dry fruits of Piper guineense on the reproductive function of adult male rats

OBJECTIVE: To study the effect of the aqueous extract of Piper guineense (Piperaceae) on male reproductive function in Wistar rats. MATERIALS AND METHODS: Male rats, 3 months old, weighing 180-210 g were administered (by gastric intubation) the aqueous extract of dry fruits of Piper guineense at two doses, 122.5 and 245 mg/kg for 8 days and 122.5 mg/kg for 55 days. The control group received distilled water for the same duration. Animals were sacrificed and the blood, testes, epididymis, seminal vesicles and prostate were collected for biochemical analyses. RESULTS: There was a significant increase in the level of testosterone in the serum and testes, cholesterol in the testes, α-glucosidase in the epididymis and fructose in the seminal vesicles after 8 days of treatment, while with 55 days of treatment, the levels of cholesterol in the testes increased by 75%, while the levels of α-glucosidase in the epididymis and the seminal vesicle fructose decreased by 24 and 21% respectively. On the other hand, there was a 20% reduction of fertility in the P. guineense-treated rats after 55 days of treatment. CONCLUSION: The aqueous extract of P. guineense at both doses (122.5 and 245 mg/kg) had a positive impact on the male reproductive function since it stimulated the secretions of the testes, epididymis and seminal vesicles. The use of P. guineense could negatively influence male fertility

Histopathologie Des Biopsies Gastriques En Milieu Africain: Etude de 142 cas à Yaoundé, Cameroun

Dans le but de contribuer à l\'étude anatomopathologique des pathologies gastriques sur des prélèvements effectués sous endoscopie, nous avons mené une étude rétrospective, transversale au service d\'anatomie et de cytologie pathologiques de l\'hôpital Gyneco-obstétrique et Pédiatrique de Yaoundé. L\'étude a porté sur 142 sujets dont 72 de sexe masculin et 70 de sexe féminin, âgés de 6 à 82 ans, avec une moyenne de 40 ans. L\'examen des coupes histologiques des biopsies après coloration à l\'hématéine-éosine et au cresyl violet a permis de recenser 172 lésions gastriques morphologiquement distinctes parmi lesquelles les gastrites sans ulcère étaient les plus représentées avec 70,93 %, suivies de l\'ulcère gastrique, 11,63%. Globalement, sur les 142 patients, la pathologie inflammatoire prédominait avec 85,92 %, la pathologie ulcéreuse représentait 14,08 %, la pathologie cancéreuse 14,78 % et les états précancéreux 6,33 %. Le taux d\'infection à Helicobacter pylori a été de 32,39 % dans l\'échantillon. Cette bactérie était associée dans 36,39 % des cas à la gastrite et dans 35,0 % des cas à l\'ulcère gastrique .Aucune prédominance par rapport au sexe n\'était relevée. La tranche d\'âge la plus représentée quelque soit la pathologie gastrique a été celle de 40-60 ans. Il ressort de notre étude que les lésions inflammatoires de la muqueuse gastrique constituent la pathologie la plus fréquente de l\'estomac. Cet état inflammatoire est parfois associé à Helicobacter pylori et aux lésions précancéreuses dont il faudrait rechercher pour en tenir compte pour le traitement.The aim of this study was to review gastric histomorphologic lesions from biopsies obtained through endoscopy and to actualise the histopathological data of gastric biopsies in the Cameroon cancer registry. It is a retrospective cross sectional study carried out in the pathology service of the Yaounde Gynaeco-Obstetric and Paediatric Hospital. The sample population consisted of 142 patients of which 72 were males and 70 females aged between 6 to 82 years (mean 40 years). Histopathological examination of biopsy specimens by the hemateine-eosine and cresyl violet staining technics revealed 172 gastric lesions, of which gastritis was most frequent (70,93 %) followed by gastric ulcers (11,63 %). Inflammatory pathology predominated with 85, 92 %, malignancy (14, 78 %) and precancerous lesions (6,33 %). The infection rate with Helicobacter pylori was 32, 39 % in the sample. This bacterium was associated with gastritis in 36, 29 % and gastric ulcers in 35 % of the samples. There was no significant statistical difference in both sexes. The most affected age group whatever the type of gastric lesion was 40-60 years. Our study reveals that gastric mucosal inflammation is the most frequent disorder of the stomach. This inflammatory state is significantly associated with Helicobacter Pylori infection and precancerous lesions and should always be investigated for, so that appropriate treatment could be instituted Keywords:Gastric biopsies – Histopathology – Yaounde – Cameroon.Clinics in Mother and Child Health Vol. 5 (2) 2008: pp. 911-91

COVID-19 and hairy-cell leukemia: An EPICOVIDEHA survey

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